Cross-linked, porous polymeric supports, such as particles, are useful as adsorbents in methods for separation and purification of organic and inorganic materials, such as in chromatographic separation and filtration methods. Further applications of such supports are e.g. as microcarriers for cell culture and as supports for solid-phase peptide or DNA synthesis. The supports should be chemically compatible to organic solvents over a wide range of pH and should have a desired shape, size, and porosity and surface area.
The porosity, and the nature of the pores, are properties that have been shown to be of specific importance in chromatographic methods for purification of target molecules, since an increased porosity will result in an increased surface area and accordingly a potentially increased binding capacity.
Furthermore, a general problem in chromatography, adsorption processes, heterogeneous catalysis etc where porous particles are used, is that the mass transport rate is strongly dependent on the particle size. Rapid mass transport can be achieved by decreasing the particle size, but small particles will also increase the backpressure of the packed beds. Hence, a trade-off must be made between the mass transport rate and the pressure-flow properties. One way to improve the mass transport in a porous particle is to increase the total pore surface. Hierarchical pore structures have for example been suggested, wherein large feeder pores from the particle surface open into a network of smaller pores with a large surface available for adsorption.
One way of providing such a pore system has been disclosed by EP 0 222 718 (Mosbach and Nilsson), which suggests to solve the above-discussed mass transport problem by introducing cavities in their particles. More specifically, EP 0 222 718 discloses a method, wherein a solid cavity-generating compound is added to an aqueous solution comprising a matrix material, emulsifier is added, particles are formed by dispersion and finally said cavity-generating compound is leached out to leave behind cavities in the particles. An illustrative cavity-generating compound is calcium carbonate, and an illustrative added amount thereof is up to 10% by weight, corresponding to 3.6% by volume. However, at such low amounts of cavity-forming compound, the pores will not make contact with each other, resulting in a closed-cell porous structure.
A specific technology for creating very small cavities in a polymer particle using a removable target compound is known as molecular imprinting. As the name implies, molecules are used as targets and are more specifically coupled to a polymeric chain via hydrogen bonding. The molecules used are for example drug targets, such as alkaloids, and the cavity left can be described as an imprint of the used target molecule and is accordingly limited to isolation of that same molecule kind. Moreover, molecular imprinting is limited to applications wherein microdimensional pore systems are desired.
U.S. Pat. No. 5,895,263 (Carter et al) discloses how materials degradable by heating can be used in a process for forming an integrated circuit device. Porous organic polysilica, which is a dielectric material, is first dissolved in a solution of a decomposable polymer. The mixture obtained is heated in order to condense the organic polysilica. Finally, the decomposable polymer is decomposed uniformly, e.g. by exposure to radiation, within the matrix of the condensed rigid organic polysilica. The product obtained has improved mechanical toughness, crack resistance and dielectric properties. Consequently, the product can also be used as a protective coating for optical articles, such as glasses, contact lenses and solar reflectors.
WO 01/09204 (Symyx Technologies) discloses a method of producing controlled-architecture polymers. More specifically, the disclosed architectured polymers are comprised of polyacrylamide repeating units having properties that are advantageous in electrophoretic separation systems, since the sieving capability of the partially branched or cross-linked polymer will be enhanced as compared to linear non-cross-linked polymers having the same repeating unit. However, sieving is not an essential property for polymer supports intended for use as chromatographic matrices, since other properties such as the above-discussed available surface area and mass transport are then of much greater importance. The method utilises living-type or semi-living type free radical polymerisation.
At the moment, free radical suspension polymerisation is the most widely used technique in the preparation of synthetic polymer supports for heterogeneous catalysts, ion exchange resins, chromatography media, peptide synthesis etc. Pore structures are then mainly provided by incorporation of a porogen and/or control of the level of cross-linking in the resin.
Atom transfer radical polymerisation (ATRP), which is a metal/ligand catalysed polymerisation, has offered a relatively new perspective on the synthesis of polymeric resins. One of the advantages with ATRP is that it provides a high degree of control over the polymerisation process. U.S. Pat. No. 5,763,548 (Matyjaszewsk et al) describes in detail conditions and components used in an ATRP process for preparing plastics, elastomers, adhesives, emulsifiers, or thermoplastic elastomers.